Osteoporosis affects 10 million people in the U.S., and the associated morbidity, mortality, and costs are significant. Screening and treatment of individuals at increased risk of osteoporotic fracture can substantially reduce fracture risk and improve health outcomes. There are multiple osteoporosis screening tests available, including dual-energy x-ray absorptiometry (DXA), risk assessment instruments, calcaneal quantitative ultrasound (QUS), and quantitative computed tomography (QCT). However, there is lack of an evidence-based consensus regarding the most effective and cost-effective population screening strategies for older women and men, specifically which tests or sequence of tests, screening initiation ages, and repeat screening intervals are best. The United States Preventive Services Task Force has identified that further research is of paramount importance to define the appropriate use of various osteoporosis screening modalities and optimal screening intervals. The goal of this proposed research is to identify best osteoporosis population screening strategies for older U.S. women and men that can be implemented to improve osteoporosis-related health outcomes. To achieve this goal, we will first systematically review the performance characteristics of risk assessment tools and QCT, whose performance characteristics are not currently well defined (Aim 1). We will then use this information, along with published data on performance of other osteoporosis screening tests (DXA and QUS), osteoporosis-related costs, and osteoporosis-related outcomes to construct comprehensive microsimulation cost-effectiveness models to compare multiple screening tests, initiation ages, and intervals for both women aged 50 and older and men aged 60 and older (Aims 2 and 3). No prior study has compared the large range of screening options we plan to compare. Our findings will include specific recommendations for clinicians and policymakers regarding osteoporosis screening strategies that can be implemented to improve health outcomes in older adults.